Participants will receive the rAd5 Env A vaccine at baseline and at Month 3.

Biological: rAd5 Env A

1 x 10^10 PU administered as 1 mL IM in deltoid

Other Name: VRC-HIVADV038-00-VP

Experimental: rAd5 Env A and rAd5 Env B

Participants will receive the rAd5 Env A vaccine at baseline and the rAd5 Env B vaccine at Month 3.

Biological: rAd5 Env A

1 x 10^10 PU administered as 1 mL IM in deltoid

Other Name: VRC-HIVADV038-00-VP

Biological: rAd5 Env B

1 x 10^10 PU administered as 1 mL IM in deltoid

Other Name: VRC-HIVADV052-00-VP

Detailed Description:

One approach to developing a preventive HIV vaccine includes the use of a prime-boost vaccine strategy. This type of strategy involves two vaccines, given sequentially at different time points. The goal is to stimulate different parts of the immune system and enhance the body's overall immune response to HIV. In this study, participants will receive two HIV vaccines 3 months apart. Heterologous-insert prime-boost vaccine regimens, which use the same gene from different HIV-1 subtypes, may be more effective than traditional homologous insert prime-boost vaccine regimens at eliciting immune responses directed at epitopes that are highly prevalent, possibly leading to a more effective immune system response to the vaccine. The purpose of this study is to assess the safety and immunogenicity of a heterologous-insert prime-boost HIV vaccine regimen that uses inserts from different HIV-1 subtypes and different adenovirus vectors.

This study will enroll healthy, HIV-uninfected people. Participants will be randomly assigned to one of five study groups:

Group 1 will receive the recombinant adenovirus serotype 35 (rAd35) Env A vaccine at baseline and the recombinant adenovirus serotype 5 (rAd5) Env A vaccine at Month 3.

Group 2 will receive the rAd35 Env A vaccine at baseline and the rAd5 Env B vaccine at Month 3.

Group 3 will receive the rAd35 Env A vaccine at baseline and at Month 3.

Group 4 will receive the rAd5 Env A vaccine at baseline and at Month 3.

Group 5 will receive the rAd5 Env A vaccine at baseline and the rAd5 Env B vaccine at Month 3.

All vaccines will be injected into the upper arm. At both vaccination study visits, participants will undergo a physical exam, a medical and medication history review, a blood and urine collection, and questionnaires. Participants will receive counseling on HIV risk reduction and pregnancy prevention. After receiving the vaccine, participants will remain in the clinic for at least 30 minutes for observation and monitoring of side effects. For 3 days after each vaccination, participants will record their temperature and side effects in a symptom log. In addition to the vaccine study visits, other study visits will occur at Week 2, two weeks after the Month 3 visit, and at Months 4, 6, and 9, at which time various study procedures will be repeated.

Participants will be contacted by study researchers once a year for 5 years for follow-up safety monitoring. Safety monitoring will not involve visiting a clinic except if a confirmatory HIV test is needed. Questions will assess health and adverse events.

The primary objective of this study is to assess the safety and tolerability, as well as the ability, of a heterologous-insert prime-boost vaccine regimen using env inserts from different HIV-1 clades to increase T-cell responses. In addition, this study is evaluating the effectiveness of a heterologous-insert prime-boost and vector prime-boost vaccine regimen at increasing T-cell responses. The study will also compare the degree of polyfunctionality of insert specific T cells after vaccination within heterologous and homologous vector vaccine regimens.

Eligibility

Ages Eligible for Study:

18 Years to 50 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Assessed by clinic staff as being "low risk" for HIV infection

Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willing to be followed for the duration of the study

Able and willing to provide informed consent

Assessment of understanding, including the completion of a questionnaire before the first vaccination and demonstration of understanding for all questionnaire items answered incorrectly

Willing to continue annual follow-up contact after the final study visit for a total of 5 years after study entry

In good general health, as shown by medical history, physical exam, and screening laboratory tests

Assessed by the clinic staff as having a low risk of HIV infection on the basis of sexual behaviors in the 12 months before study entry. More information on this criterion can be found in the protocol.

Adenovirus 5 nAb titer less than 1:18

Adenovirus 35 nAb titer less than 1:12

Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female and greater than or equal to 13.0 g/dL for participants who were born male

White blood cell (WBC) count between 3,300 to 12,000 cells/mm^3

Total lymphocyte count greater than or equal to 800 cells/mm^3

Remaining differential either within site's normal range or with site physician approval

Platelet level between 125,000 to 550,000/mm^3

Alanine aminotransferase (ALT) less than or equal to 1.25 times the site's upper limit of normal

Participants who were born female must have a negative pregnancy test result before the first study vaccination

Participants who were born female must agree to use an effective form of contraception from at least 21 days before study entry until the last study visit. More information on this criterion can be found in the protocol.

Participants who were born female must agree not to seek pregnancy through alternative methods (e.g., artificial insemination, in vitro fertilization) until after the last study visit

If born male, must be fully circumcised (as documented at screening examination)

Exclusion Criteria:

Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or use of any other illicit drugs in the 12 months before study entry

Any medical, psychiatric, occupational, or other condition that would interfere with participation in the study

Serious adverse reactions to vaccines, including anaphylaxis and related symptoms (e.g., hives, respiratory difficulty, angioedema, abdominal pain). A person who had an adverse reaction to the pertussis vaccine is not excluded.

Autoimmune disease or immunodeficiency

Active syphilis infection

Asthma, other than mild well-controlled asthma. More information on this criterion can be found in the protocol.

Type 1 or type 2 diabetes mellitus, including cases controlled with diet alone. People with a history of gestational diabetes are not excluded.

Surgical removal of the thyroid or thyroid disease requiring medication in the 12 months before study entry

Angioedema in the 3 years before study entry or angioedema requiring medication in the 2 years before study entry

High blood pressure that is not well controlled or high blood pressure of 150/100 mm Hg or greater at study entry. More information on this criterion can be found in the protocol.

Body mass index (BMI) greater than or equal to 40, or BMI greater than or equal to 35 and two or more of the following conditions: age greater than 45, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, or known hyperlipidemia

Cancer. People with surgically removed cancer, that in the opinion of the investigator, is unlikely to recur during the study period are not excluded.

Seizure disorder. People with a history of seizures who have not required medications or had a seizure within the 3 years before study entry are not excluded.

Absence of the spleen

Psychiatric condition that makes study compliance difficult (e.g., people with psychoses in the 3 years before study entry, ongoing risk for suicide, history of suicide attempt in the 3 years before study entry)

Pregnant or breastfeeding

Has been circumcised within 90 days prior to first vaccination or displays evidence that surgical site is not fully healed

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01095224